Genetic Variant NM_173353.4:c.609-10868A>G (chr12-71961651-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_173353.4(TPH2):c.609-10868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,352,100 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 73 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 49 hom. )

Consequence

TPH2
NM_173353.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.302

Publications

1 publications found

Variant links:

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

TPH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4 link	c.609-10868A>G		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2	Q8IWU9-1
TPH2	XR_001748575.2 link	n.849A>G		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4 link	c.609-10868A>G		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3		Q8IWU9-1
TPH2	ENST00000546576.1 link	n.717A>G		non_coding_transcript_exon_variant	Exon 6 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2511

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00388

AC:

890

AN:

229138

AF XY:

0.00280

show subpopulations

Gnomad AFR exome

AF:

0.0577

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000568

Gnomad OTH exome

AF:

0.00154

GnomAD4 exome

AF:

0.00152

AC:

1822

AN:

1199780

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

758

AN XY:

594954

show subpopulations

African (AFR)

AF:

0.0603

AC:

1585

AN:

26288

American (AMR)

AF:

0.00190

AC:

AN:

37278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16896

East Asian (EAS)

AF:

0.00

AC:

AN:

16800

South Asian (SAS)

AF:

0.000108

AC:

AN:

83214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17190

Middle Eastern (MID)

AF:

0.00157

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

953736

Other (OTH)

AF:

0.00260

AC:

114

AN:

43906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

193

290

386

483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0165

AC:

2512

AN:

152320

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

1171

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0578

AC:

2404

AN:

41560

American (AMR)

AF:

0.00497

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68020

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

118

236

354

472

590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00929

Hom.:

Bravo

AF:

0.0188

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

(source)

DANN

Benign

0.63

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over